While several risk factors for colorectal cancer are known, because they confer low relative risk they are not extremely useful in identifying groups of individuals at high risk for this disease. The ability to identify such groups would allow colorectal cancer prevention and early detection research to be more targetted. Recently, researchers reported finding elevated levels of ornithine decarboxylase (ODC) in normal appearing mucosae of polyp bearing afflicted individuals with familial polyposis and in half of nonpolyp-bearing, possibly afflicted offspring of afflicted individuals. ODS is the first and rate limiting enzyme in the polyamine biosynthetic pathway. Various evidence suggests that it may be an important component in tumor promotion. We have developed procedures for studying ODC in 2 mm forceps biopsies of human colonic mucosae and 3 mm punch biopsies of human skin. In preliminary studies we have found large variations in ODC activity levels in these tissues in different individuals. As a first step to clarifying the significance of these variations we propose to carefully study differences in ODC activity in different groups. We will study basal (colon mucosae) and basal and in vitro 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced ODC activity in tissues from healthy, family history of cancer free, non cancer and non adenoma bearing individuals and compare these ODC activity levels to those found in the same tissues in 6 groups of individuals at increased risk for colorectal cancer. The six groups will be 1) members of family with nonpolyposis hereditary colon cancer; 2) individuals with a family history of colorectal cancer in a single relative; 3) individuals with a personal history of colorectal cancer; 4) individuals with a personal history of breast, uterine, ovary, or prostate cancer; 5) individuals with at least one colorectal adenoma; and 6) individuals with ulcerative colitis. We will also determine whether there is a correlation between age and ODC activity levels in these tissues. At the conclusion of this research, we should have adequate data to say whether differences in mean ODC activity levels suggest that ODC is a useful marker in groups of persons at increased risk for colorectal cancer worthy of large scale performance measure (sensitivity and specificity) studies.